Cryo-EM structures of human hepatitis B and woodchuck hepatitis virus small spherical subviral particles.

Cryo-EM structures of human hepatitis B and woodchuck hepatitis virus small spherical subviral particles.
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人乙肝病毒和土拨鼠肝炎病毒小球形亚病毒颗粒的冷冻-EM结构。

DOI:
10.1126/sciadv.abo4184
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发表时间:
2022-08-05
期刊:
影响因子:
13.6
通讯作者:
--
中科院分区:
综合性期刊1区
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--
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可检测到的乙肝表面抗原的丢失被认为是慢性乙肝的一种功能性治愈方法。当然,乙肝表面抗原可以被整合到病毒粒子的包膜中,或者与宿主细胞中的脂质一起组装成亚病毒颗粒(SVPs)。到目前为止,还没有关于乙肝表面抗原的详细结构,已发表的SVP结构也存在争议。在这里,我们首次报道了由冷冻电子显微镜结合AlphaFold2预测确定的乙肝病毒(乙肝病毒)及其相关土拨鼠肝炎病毒(WHV)球形SVP的亚纳米分辨率结构。这两种结构都表现出独特的菱形双八面体对称性,24个突起的尖峰由带有4个螺旋结构域的小HBs Ag二聚体组成。SVP中的脂质部分被组织成非规范的脂膜而不是脂双层,这可以调节暴露的疏水表面并调节颗粒的稳定性。综上所述,这些发现促进了我们对病毒膜组织以及乙肝病毒和WHV球形SVP结构的了解。庚型核糖核酸病毒球形亚病毒颗粒的高分辨率结构显示了独特的脂肪和蛋白质结构。
The loss of detectable hepatitis B surface antigen (HBsAg) is considered a functional cure in chronic hepatitis B. Naturally, HBsAg can be incorporated into the virion envelope or assembled into subviral particles (SVPs) with lipid from host cells. Until now, there has been no detailed structure of HBsAg, and the published SVP structures are controversial. Here, we report the first subnanometer-resolution structures of spherical SVP from hepatitis B virus (HBV) and the related woodchuck hepatitis virus (WHV) determined by cryo–electron microscopy in combination with AlphaFold2 prediction. Both structures showed unique rhombicuboctahedral symmetry with 24 protruding spikes comprising dimer of small HBsAg with four helical domains. The lipid moiety in the SVP is organized in a noncanonical lipid patch instead of a lipid bilayer, which can accommodate the exposed hydrophobic surface and modulate particle stability. Together, these findings advance our knowledge of viral membrane organization and the structures of HBV and WHV spherical SVPs. High-resolution structures of hepadnavirus spherical subviral particles show unique lipid and protein organization.
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